作者: Aileen dela Peña , Isabelle Leclercq , Jacqueline Field , Jacob George , Brett Jones
DOI: 10.1053/J.GASTRO.2005.09.004
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摘要: Background& Aims: We explored the roles of nuclear factor-kappa B (NF-kappa B) and tumor necrosis factor (TNF) alpha (TNF-alpha) as mediators inflammation in a nutritional model steatohepatitis. Methods: Wild-type (wt), TNF null (-/-), receptor (R)-1-/- mice were fed methionine- choline-deficient (MCD) diet for up to 5 weeks. Liver injury (serum alanine aminotransferase [ALT]), hepatic inflammation, triglycerides, lipid peroxide levels determined. Hepatic NF-kappa activation expression intercellular adhesion molecule-1 (ICAM-1) assayed. Results: Irrespective genotype, MCD diet-fed developed peroxidation serum ALT elevation; at day 10, livers from wt, TNF-/-, TNFR-1-/- showed equivalent B/DNA binding was enhanced fractions wt compared with dietary controls; there corresponding increases ICAM-1 messenger RNA (mRNA). Likewise, by feeding TNF-/- respective controls. To establish whether is primary mediator experimental steatohepatitis, we overexpressed mutant, nondegradable I kappa (mI B), delivered adenovirus vivo. As expected, mI reduced induced feeding, resultant abrogation synthesis. Such blockade transcriptional substantially protected against development significant reductions liver inflammation. Conclusions: In activated early an important proinflammatory lesion development, but steatohepatitis occurs independently synthesis TNFR-1 activation.